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Cerebrospinal fluid cytokines after autologous haematopoietic stem cell transplantation and intrathecal rituximab treatment for multiple sclerosis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.ORCID iD: 0000-0002-7045-1806
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.ORCID iD: 0000-0003-0934-4478
Karolinska Inst, Dept Clin Sci, Danderyd Hosp, SE-17177 Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.ORCID iD: 0000-0003-0226-1047
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2023 (English)In: Brain Communications, E-ISSN 2632-1297, Vol. 5, no 1, article id fcad011Article in journal (Refereed) Published
Abstract [en]

Multiple sclerosis has been established as an inflammatory disease of the central nervous system. Many aspects of the pathophysiology are still unknown and it is presently unclear how different treatments affect the immunopathology of multiple sclerosis. In this study, we explored cytokines discriminating between individuals with multiple sclerosis and healthy controls and then how these cytokines were affected by treatment intervention with autologous haematopoietic stem cell transplantation or intrathecal rituximab. CSF from individuals with multiple sclerosis and healthy controls were analysed with a proximity extension assay to simultaneously determine the level of 92 cytokines and other inflammation-related proteins. In total, CSF from 158 multiple sclerosis patients and 53 healthy controls were analysed. Sixty-four patients with relapsing-remitting multiple sclerosis and 27 with progressive multiple sclerosis took part in a cross-sectional study and underwent lumbar puncture on a single occasion. Forty-five patients with relapsing-remitting multiple sclerosis were treated with autologous haematopoietic stem cell transplantation and underwent lumbar puncture at baseline and then at follow-up visits made at 1-, 2- and 5 years. Twenty-two patients with progressive multiple sclerosis were treated with intrathecal rituximab and followed with lumbar punctures at baseline and then at follow-up visits made at 3-, 6- and 12 months. Of the 92 studied cytokines, 16 were found to be altered in multiple sclerosis and 11 were decreased after treatment with autologous haematopoietic stem cell transplantation. None of the studied cytokines was affected by treatment with intrathecal rituximab for progressive multiple sclerosis. Some proteins were highly associated with each other. Therefore, a cluster analysis was made and then the highest-ranked protein from the four highest-ranked clusters was used for the subsequent analyses. CCL3, IL-12B, CXCL10 and IL-8 discriminated between multiple sclerosis patients and controls, but only IL-12B differed between patients with relapsing-remitting and progressive multiple sclerosis. The CSF concentrations of CCL3, IL-12B and CXCL10 were decreased after autologous haematopoietic stem cell transplantation, whereas IL-8 appeared to be unaffected by this intervention. High concentrations of IL-8 were associated with worse outcome in both treatment groups. Overall, the results suggest a profound effect of autologous haematopoietic stem cell transplantation on the inflammatory milieu of the CSF in multiple sclerosis. Burman et al. measured CSF concentrations of 92 cytokines in patients with multiple sclerosis. CCL3, IL-12B, CXCL10 and IL-8 discriminated best between patients and healthy controls. The CSF concentrations of CCL3, IL-12B and CXCL10 decreased after treatment intervention with autologous haematopoietic stem cell transplantation for relapsing-remitting multiple sclerosis.

Place, publisher, year, edition, pages
Oxford University Press, 2023. Vol. 5, no 1, article id fcad011
Keywords [en]
multiple sclerosis, cytokines, autologous haematopoietic stem cell transplantation, rituximab, CSF
National Category
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-497706DOI: 10.1093/braincomms/fcad011ISI: 000928584000002PubMedID: 36756308OAI: oai:DiVA.org:uu-497706DiVA, id: diva2:1742535
Funder
Swedish Research Council, 2021-02814Swedish Research Council, 2021-02189Insamlingsfonden Bissen BrainwalkMarianne and Marcus Wallenberg FoundationSwedish Society of Medicine, SLS-726341Swedish Society for Medical Research (SSMF)Available from: 2023-03-09 Created: 2023-03-09 Last updated: 2023-03-09Bibliographically approved

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Burman, JoachimZhukovskaja, ChristinaFreyhult, EvaWiberg, AnnaKultima, Kim
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